This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Human 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) is an ER-localized membrane protein that catalyzes the interconversion of cortisone and cortisol. In adipose tissue, excessive cortisol production through 11beta-HSD1 activity has been implicated in the pathogenesis of type II diabetes and obesity, which makes this enzyme a potential drug target against these diseases. Recently we have solved the first high-resolution crystal structure of the extracellular portion of the enzyme. We wish to undertake further studies on 11beta-HSD1 with regards to enzyme oligomerization and reductase activity. To this end, we would like to carry out systematic truncations of the C-terminus and use x-ray crystallography to understand the structural features controlling these two interrelated functions.